The objective of the proposed program is to obtain sufficient basic knowledge so that in vivo methodology can be applied to the synchronization of a large proportion of the cells of several mouse tumors in their phase of the cell cycle during predictable periods of time, rendering the tumor more sensitive to specific chemotherapy or radiation therapy, while minimizing drug toxicity to normal rapidly replicating tissues. The cell cycle kinetics of several mouse tumors will be determined. Using techniques that have been developed in this laboratory, it is proposed to intravenously infuse hydroxyurea into the tumor bearing mice in such a fashion that death of normal tissues from unbalanced growth will be small, and the predominant cell cycle phase of the tumor tissue will be different from that of the more drug sensitive normal tissues during known intervals of time. Chemotherapy or radiation therapy will then be administered during tumor-sensitive periods and tumor response and animal survival will be evaluated.